sFLT01 modulates invasion and metastasis in prostate cancer DU145 cells by inhibition of VEGF/GRP78/MMP2&9 axis
Abstract Background About 90% of cancer-related deaths are due to metastasis of cancer cells, and angiogenesis is a critical step in this process. sFLT01 is a novel fusion protein and a dual-targeting agent that neutralizes both VEGF and PlGF proangiogenic activities. GRP78 dual effect in tumor grow...
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| Format: | Article |
| Language: | English |
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BMC
2021-05-01
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| Series: | BMC Molecular and Cell Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12860-021-00367-5 |
| _version_ | 1818939741295345664 |
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| author | Sepideh Taghizadeh Zahra-Soheila Soheili Mehdi Sadeghi Shahram Samiei Ehsan Ranaei Pirmardan Ali Kashanian Fahimeh Zakeri Hamid Latifi-Navid Hoda Shams Najafabadi |
| author_facet | Sepideh Taghizadeh Zahra-Soheila Soheili Mehdi Sadeghi Shahram Samiei Ehsan Ranaei Pirmardan Ali Kashanian Fahimeh Zakeri Hamid Latifi-Navid Hoda Shams Najafabadi |
| author_sort | Sepideh Taghizadeh |
| collection | DOAJ |
| description | Abstract Background About 90% of cancer-related deaths are due to metastasis of cancer cells, and angiogenesis is a critical step in this process. sFLT01 is a novel fusion protein and a dual-targeting agent that neutralizes both VEGF and PlGF proangiogenic activities. GRP78 dual effect in tumor growth and angiogenesis could be activated under VEGF stimulation. The current study was designed to investigate the inhibitory impact of sFLT01 protein on VEGF/GRP78 axis. To this point, sFLT01 construct was synthesized, recombinant plasmid was expressed in eukaryotic host cells, sFLT01-HisTag protein was extracted and analyzed. The functional activity of sFLT01 on VEGF-enhanced tube formation and angiogenesis of HUVEC cells were examined. Eventually, the inhibitory impact of sFLT01 on growth, invasiveness, and migration of human prostate cancer cell line, DU145, was assessed. Real-time PCR evaluated the level of GRP78 and its effect on the downstream factors; matrix metallopeptidase proteins 2&9 (MMP2&9) along with tissue inhibitor of metalloproteinase proteins1&2 (TIMP1&2) under sFLT01 stimulation. Results According to the data, sFLT01 protein showed modulatory impact on proliferation, invasion, and migration of DU145 cells along with the potential of HUVECs angiogenesis. Real-Time PCR analysis depicted a significant downregulation in GRP78, MMP2 and MMP9 transcripts’ levels, and a subsequent elevation of TIMP1 and TIMP2 expression under sFLT01 stimulation was detected. Conclusion Overall, these data indicated that the inhibitory impact of sFLT01 on cancer cells growth and invasiveness could be mediated through the modulation of VEGF/GRP78/MMP2&9 axis and activation of TIMPs. |
| first_indexed | 2024-12-20T06:28:34Z |
| format | Article |
| id | doaj.art-a38033b4020549c5bc23682ad23605ca |
| institution | Directory Open Access Journal |
| issn | 2661-8850 |
| language | English |
| last_indexed | 2024-12-20T06:28:34Z |
| publishDate | 2021-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Molecular and Cell Biology |
| spelling | doaj.art-a38033b4020549c5bc23682ad23605ca2022-12-21T19:50:13ZengBMCBMC Molecular and Cell Biology2661-88502021-05-0122111110.1186/s12860-021-00367-5sFLT01 modulates invasion and metastasis in prostate cancer DU145 cells by inhibition of VEGF/GRP78/MMP2&9 axisSepideh Taghizadeh0Zahra-Soheila Soheili1Mehdi Sadeghi2Shahram Samiei3Ehsan Ranaei Pirmardan4Ali Kashanian5Fahimeh Zakeri6Hamid Latifi-Navid7Hoda Shams Najafabadi8Department of Molecular Medicine, National Institute of Genetic Engineering and BiotechnologyDepartment of Molecular Medicine, National Institute of Genetic Engineering and BiotechnologyDepartment of Molecular Medicine, National Institute of Genetic Engineering and BiotechnologyBlood Transfusion Research Center, High Institute for Research and Education in Transfusion MedicineMolecular Biomarkers Nano-Imaging Laboratory, Brigham and Women’s Hospital, Department of Radiology Harvard Medical SchoolDepartment of Molecular Medicine, National Institute of Genetic Engineering and BiotechnologyDepartment of Molecular Medicine, National Institute of Genetic Engineering and BiotechnologyDepartment of Molecular Medicine, National Institute of Genetic Engineering and BiotechnologyDepartment of Molecular Medicine, National Institute of Genetic Engineering and BiotechnologyAbstract Background About 90% of cancer-related deaths are due to metastasis of cancer cells, and angiogenesis is a critical step in this process. sFLT01 is a novel fusion protein and a dual-targeting agent that neutralizes both VEGF and PlGF proangiogenic activities. GRP78 dual effect in tumor growth and angiogenesis could be activated under VEGF stimulation. The current study was designed to investigate the inhibitory impact of sFLT01 protein on VEGF/GRP78 axis. To this point, sFLT01 construct was synthesized, recombinant plasmid was expressed in eukaryotic host cells, sFLT01-HisTag protein was extracted and analyzed. The functional activity of sFLT01 on VEGF-enhanced tube formation and angiogenesis of HUVEC cells were examined. Eventually, the inhibitory impact of sFLT01 on growth, invasiveness, and migration of human prostate cancer cell line, DU145, was assessed. Real-time PCR evaluated the level of GRP78 and its effect on the downstream factors; matrix metallopeptidase proteins 2&9 (MMP2&9) along with tissue inhibitor of metalloproteinase proteins1&2 (TIMP1&2) under sFLT01 stimulation. Results According to the data, sFLT01 protein showed modulatory impact on proliferation, invasion, and migration of DU145 cells along with the potential of HUVECs angiogenesis. Real-Time PCR analysis depicted a significant downregulation in GRP78, MMP2 and MMP9 transcripts’ levels, and a subsequent elevation of TIMP1 and TIMP2 expression under sFLT01 stimulation was detected. Conclusion Overall, these data indicated that the inhibitory impact of sFLT01 on cancer cells growth and invasiveness could be mediated through the modulation of VEGF/GRP78/MMP2&9 axis and activation of TIMPs.https://doi.org/10.1186/s12860-021-00367-5Prostate cancerAngiogenesissFLT01VEGFGRP78 |
| spellingShingle | Sepideh Taghizadeh Zahra-Soheila Soheili Mehdi Sadeghi Shahram Samiei Ehsan Ranaei Pirmardan Ali Kashanian Fahimeh Zakeri Hamid Latifi-Navid Hoda Shams Najafabadi sFLT01 modulates invasion and metastasis in prostate cancer DU145 cells by inhibition of VEGF/GRP78/MMP2&9 axis BMC Molecular and Cell Biology Prostate cancer Angiogenesis sFLT01 VEGF GRP78 |
| title | sFLT01 modulates invasion and metastasis in prostate cancer DU145 cells by inhibition of VEGF/GRP78/MMP2&9 axis |
| title_full | sFLT01 modulates invasion and metastasis in prostate cancer DU145 cells by inhibition of VEGF/GRP78/MMP2&9 axis |
| title_fullStr | sFLT01 modulates invasion and metastasis in prostate cancer DU145 cells by inhibition of VEGF/GRP78/MMP2&9 axis |
| title_full_unstemmed | sFLT01 modulates invasion and metastasis in prostate cancer DU145 cells by inhibition of VEGF/GRP78/MMP2&9 axis |
| title_short | sFLT01 modulates invasion and metastasis in prostate cancer DU145 cells by inhibition of VEGF/GRP78/MMP2&9 axis |
| title_sort | sflt01 modulates invasion and metastasis in prostate cancer du145 cells by inhibition of vegf grp78 mmp2 9 axis |
| topic | Prostate cancer Angiogenesis sFLT01 VEGF GRP78 |
| url | https://doi.org/10.1186/s12860-021-00367-5 |
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